eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Toluene

Author: Nathanael J McKeown, DO, Assistant Professor, Oregon Health and Science University; Medical Toxicologist, Oregon Poison Center; Attending Physician, Emergency Medicine, Portland Veteran Affairs Medical Center, Oregon Health and Science University
Contributor Information and Disclosures

Updated: May 20, 2009

Introduction

Background

Toluene (methylbenzene, toluol, phenylmethane) is an aromatic hydrocarbon (C₇ H₈) commonly used as an industrial solvent for the manufacturing of paints, chemicals, pharmaceuticals, and rubber. It is identified as CAS#108-88-3, and the United Nations Department of Transportation's number for toluene is UN#1294.

Toluene is found in gasoline, acrylic paints, varnishes, lacquers, paint thinners, adhesives, glues, rubber cement, airplane glue, and shoe polish. At room temperature, toluene is a colorless, sweet smelling, and volatile liquid.

Toxicity can occur from unintentional or deliberate inhalation of fumes, ingestion, or transdermal absorption. Toluene abuse or "glue sniffing" has become widespread, especially among children or adolescents, because it is readily available and inexpensive. Toluene is commonly abused by saturating or soaking a sock or rag with spray paint, placing it over the nose and mouth, and inhaling to get a sensation of euphoria, buzz, or high. Slang names for inhalation include huffing (ie, soaking a sock or rag) and bagging (ie, spraying paint into a plastic bag and inhaling). With bagging, exhaled air is rebreathed and resulting hypoxia and hypercarbia may add to the disorienting effects of the solvent.

The Occupational Safety and Health Administration (OSHA) has determined the acceptable level of occupational exposure to toluene for people in the workplace. The Permissible Exposure Limit (PEL) of 200 ppm is considered an acceptable level of exposure as a time-weighted average for an 8-hour workday.¹ Toluene levels of 500 ppm are considered immediately dangerous to life and health. 

Due to genetic polymorphisms, some people may be more sensitive to the effects of inhaled solvents than others.²  Occupational asthma has occurred in some workers exposed to toluene levels considered safe in the workplace. For such people, protective equipment should be used and provided by employers, even when toluene levels are in the acceptable range.

Workers with a history of asthma induced by solvent exposure should also be warned about and protected from short-term exposure to higher concentrations. The duration of the exposure, not just the level, may also contribute to asthma exacerbations, and should be monitored. 

Pathophysiology

Toluene is highly lipophilic, which accounts for its primary effects on the central nervous system (CNS). After crossing the blood-brain barrier, toluene, along with other volatile anesthetic agents, had been previously thought to inhibit neuronal transmission by causing a change in membrane or membrane protein conformation. Recent research has shown that interactions with several key brain neurotransmitters, mainly γ-aminobutyric acid_A (GABA), to a lessor degree glycine, and possibly dopamine, are responsible for the clinical effects seen.³ Postmortem studies along with magnetic resonance imaging (MRI) findings have shown diffuse white matter demyelination and gliosis (solvent vapor/toluene leukoencephalopathy), which is postulated to be the end product by which chronic toxicity occurs, although the exact mechanism by which this occurs remains unclear.⁴

Central nervous system

Acute intoxication from inhalation is characterized by rapid onset of CNS symptoms including euphoria, hallucinations, delusions, tinnitus, dizziness, confusion, headache, vertigo, seizures, ataxia, stupor, and coma.

Chronic CNS sequelae include neuropsychosis, cerebral and cerebellar degeneration with ataxia, seizures, choreoathetosis, optic and peripheral neuropathies, decreased cognitive ability, anosmia, optic atrophy, blindness, ototoxicity, and deafness.

Cardiopulmonary

Toluene has direct negative effects on cardiac automaticity and conduction and can sensitize the myocardium to circulating catecholamines. "Sudden sniffing death" secondary to cardiac arrhythmias has been reported. Pulmonary effects include bronchospasm, asphyxia, acute lung injury (ALI), and aspiration pneumonitis.

Gastrointestinal 

GI symptoms from inhalation and ingestion may result in abdominal pain, nausea, vomiting, and hematemesis. Hepatotoxicity manifests with ascites, jaundice, hepatomegaly, and liver failure. A rare form of hepatitis—hepatic reticuloendothelial failure (HREF)—has been reported with toluene exposure.⁵ With the widespread abuse of volatile substances in young adults today, hepatitis secondary to toluene toxicity, not just infectious causes, should be considered in the differential diagnosis in the younger patient population who present with concerning findings.

Renal and metabolic

Reported renal toxicity from toluene exposure includes renal tubular acidosis (RTA), hypokalemia, hypophosphatemia, hyperchloremia, azotemia, sterile pyuria, hematuria, and proteinuria.

Hematologic

Hematologic consequences of exposure may include lymphocytosis, macrocytosis, eosinophilia, hypochromia, and basophilic stippling, and in severe cases, aplastic anemia.  

Dermatologic

Cutaneous contact with skin may range in severity from dermatitis to extensive chemical burns with coagulation necrosis.

Musculoskeletal

Toluene can affect skeletal muscles directly, resulting in rhabdomyolysis and myoglobinemia. Profound hypokalemia due to RTA can produce severe muscle weakness mimicking Guillain-Barré syndrome. In animal studies, chronic inhalational exposure to toluene was found to affect bone metabolism, contributing to bone resorption and inhibition of bone formation.⁶

Frequency

United States

Solvents including glue are easily accessible and inexpensive, making them a frequently abused substance. Glue sniffing is most frequently observed in teenagers and young adults in lower economic groups. According to the National Survey on Drug Use and Health in 2007, approximately 775,000 people were new inhalant users.⁷ Almost 23.5 million people older than12 years reported trying an inhalant at least once. An estimated 3-4% of American teenagers engage in sniffing on a regular basis, and 7-12% of high school students have tried sniffing at least once.

Chronic nonintentional exposure also occurs among people in the painting, gasoline, chemical, and rubber industries. The 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data Systems records only 1077 exposures to toluene and xylene combined.⁸ Of these, only 5 sustained major adverse outcomes, and 1 death was reported. This report severely underestimates the abuse of this agent.

International

Solvent abuse is a popular practice around the world. In the United Kingdom, 3.5-10% of children younger than 13 years have abused volatile substances, and 0.5-1% are long-term users.⁹ In Brazil, 6.1% of the population older than 12 years report trying an inhalant at least once.¹⁰ In low-income families in Sao Paulo, Brazil, 24% of children had inhaled a volatile substance at some time and 4.9% had inhaled within the last month.

In Singapore, toluene glue sniffing has reached epidemic proportions.¹¹ In 1980, 24 cases of solvent abuse were reported. By 1984, this number had increased to 763. From 1987-1991, 1781 glue sniffers were identified.

In 2005, it was reported that street children in India were abusing typewriter eraser fluid, which contains toluene; the patients cited easy access, affordability, and a regular "high" as reasons for usage.¹²

In Australia, 22% of 12-year-olds reported lifetime use of inhalants, decreasing to 15% by age 15 and 11% by age 17.¹³

Mortality/Morbidity

Sudden death is the most serious risk from inhalation of toluene or other volatile substances. Four direct modes of toxicity leading to death from toluene and other inhaled substances are anoxia, respiratory depression, vagal stimulation, and, most importantly, cardiac arrhythmias. Trauma, aspiration, and asphyxia from plastic bag use are contributing factors to mortality from solvent abuse.

Volatile substance abuse sensitizes the myocardium to circulating catecholamines. Sudden alarm, exercise, sexual activity, or any kind of startling (eg, parents, police) may induce arrhythmias. In many cases of death associated with solvent abuse, fright and running were the immediate antemortem events.

Prolonged exposure to toluene by inhalation is associated with CNS, heart, liver, kidney, and lung damage. Other sequelae include muscle weakness, nasal ulcerations, recurrent epistaxis, chronic rhinitis, neuropsychiatric abnormalities, GI symptoms, and peripheral neuropathies (see Pathophysiology).

• In the 1960s, a total of 110 cases of sudden death from solvent abuse were reported in the United States. In a review of death records in Virginia from 1987-1996, 39 deaths related to solvent abuse were identified. Males accounted for 95% of cases with the majority (70%) of deaths occurring at age 22 or younger.¹⁴  One death was reported to be an occupational exposure. In Texas, a 10-year review of death certificates identified 144 people in whom inhalants were a contributing factor. The majority were male (92%), white (81%), with a mean age of 25.6 years.¹⁵
• In 1988, in the United Kingdom, 133 deaths were reported in people aged 11-76 years and from varying social backgrounds; 72% of these deaths occurred in adolescents, and 90% of deaths occurred in males.⁹
• In Singapore, from 1983-1991, 33 people were found to have toluene in their blood postmortem; 22 were known glue sniffers; 11 were suspected of solvent abuse; 6.1% of deaths were from acute toluene poisoning; and 87.9% were associated with falling, drowning, or jumping, which suggests a correlation between the intoxicating effect of toluene and the high incidence of traumatic death of its users.¹¹
• From 1983-1991, 4 deaths attributed to occupational exposures were reported in Singapore.¹¹
• In a 20-year retrospective review of autopsy cases in Australia, 0.2% were attributed to inhalant use, with the majority (92%) being male.¹⁶

Race

No scientific data indicate that outcomes of toluene exposure are based on race.

Sex

Although typically thought of as an activity of young males (most mortalities occur in young males), epidemiologic studies more than 20 years ago showed more than 50% of chronic solvent abusers were females in their prime childbearing years.¹⁵ A more recent report in 2006 in Florida showed higher rates among females compared to males in high school for lifetime and current use.

Age

Toluene inhalation is found in people of all ages.

• Most acute cases occur in young males aged 11-19 years who participate in glue sniffing as a group activity.
• Cases have been reported in people aged in their 50s and 60s.

Clinical

History

Determining a history of toluene exposure or risk of exposure on admission is important, as well as the the route of exposure, whether inhalation, ingestion, or transdermal absorption. 

• History of huffing or bagging before presentation or history of previous abuse of inhalants
• History of other drugs that may be in the patient's system, including alcohol (ETOH), cocaine, and marijuana
  • Toluene intoxication has a similar presentation to alcohol intoxication.
  • Alcohol inhibits the metabolism of toluene and raises the concentration of toluene in the blood 2-fold.
  • Cocaine, or any sympathomimetic use, may increase risks of fatal arrhythmias.
• History of workers' occupations (eg, painters, chemists, textile workers, gasoline refinery workers, rubber industry workers) to assess whether workers may have had nonintentional acute or chronic exposure and may be at risk
• Hobbies or activities that lead to nonintentional or intentional exposure
  • Model airplane glues and rubber cements are sources of toluene.
  • Varnishes may affect people refinishing wooden furniture.
• Toxicities and risks that vary with routes of exposure
  • Ingestion may cause hematemesis and abdominal pain.
  • Inhalation is a risk for airway compromise secondary to aspiration and induction of bronchospasm; subsequent hypoxemia from chemical pneumonitis and acute lunge injury also may occur.
  • Cutaneous exposure may result in coagulation necrosis without copious skin irrigation.

Physical

Physical examination is an important aid in confirming a suspected diagnosis of toluene poisoning. Patients with acute toluene poisoning may present with a range of pulmonary and CNS symptoms depending on duration, route of exposure, and level of toluene in the air or liquid.

Patients with chronic exposure may present with wide variety of complaints.

• General/vitals
  • Patients may be tachypneic, tachycardic, and hypoxic on initial evaluation.
  • Hypotension may be present.
  • Fever may be present, secondary to aspiration pneumonitis.
  • Sweet smelling odor: Hair, breath, and clothing may smell of solvent. Twenty percent of inhaled toluene is expired from the lungs unchanged.
  • Paint or oil stains may be seen on clothing.
• Head, eyes, ears, nose, and throat (HEENT)
  • "Huffer's eczema": Perioral defatting dermatitis secondary to contact of solvent vapors with skin may be noted.
  • Mucosal irritation (eg, burning mouth, eyes, throat)
  • Injected sclera
  • Nystagmus
• Neurologic
  • Decreased level of consciousness leading to coma
  • Dizziness and headaches
  • Confusion
  • Hallucinations
  • Amnesia
  • Seizure activity
  • Paresthesias (Toluene has anesthetic effects.)
  • Decreased deep tendon reflexes
  • Cerebellar signs  
    • Decreased motor coordination
    • Impaired fine motor movements
    • Ataxia
    • Balance problems
    • Anesthesia
• Pulmonary
  • Respiratory distress
  • Dyspnea
  • Chest pain (with aspiration)
  • Tachypnea
  • Cyanosis
  • Wheezing from bronchospasm
• Gastrointestinal
  • Nausea
  • Vomiting
  • Abdominal pain
  • Hematemesis
  • Jaundice
• Dermatologic
  • Itching or burns from skin contact
  • Glue sniffer's rash (see in HEENT)
• Musculoskeletal: Profound muscle weakness due to hypokalemia; muscle pain

Causes

• Inhalation of airborne toluene is the most common cause of exposure.
• Exposure can occur in several occupations including paint workers, dye makers, and workers in the chemical and petrochemical industry.
• Toluene toxicity can occur from the following:
  • Nonintentional or deliberate inhalation of fumes
  • Ingestion
  • Absorption through the skin
• Toluene is found in the following:
  • Gasoline
  • Acrylic paints
  • Varnishes
  • Lacquers
  • Paint thinners
  • Adhesives
  • Glues
  • Rubber cement
  • Airplane glue
  • Shoe polish
  • Typewriter erasing fluid

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